Dengue fever is caused by any of four serotypes of dengue virus, dengue-1, dengue-2, dengue-3, and dengue-4, which are transmitted to humans by mosquitoes. In adults, dengue infections typically cause self-limited but incapacitating acute illness with fever, muscle pains, headache and an occasional rash. The illness may be complicated by hemorrhagic fever, which may be manifested by a positive tourniquet test, spontaneous petechiae, frank bleeding, and/or shock. Dengue-hemorrhagic fever is fatal in about 0.5% of cases. Patients who have antibody from an earlier dengue infection who are subsequently infected by another dengue strain have been shown to be at higher risk for dengue hemorrhagic fever.
The mosquito vectors of dengue viruses are found in all tropical and sub-tropical areas of the world and in some temperate areas of the United States, Europe, Africa, and the Middle East. In recent years, endemic and epidemic dengue infections have occured in Central and South Ameria, Southeast Asia, India, Africa, the Caribbean and Pacific regions. Vector control is impractical.
An effective vaccine is needed which should confer protection against all four serotypes of dengue.
The present invention satisfies the need discussed above. The present invention relates to vaccine compositions comprising attenuated dengue virus from all four serotypes. The attenuated virus is provided in an amount sufficient to induce an immune response in a human host, in conjuction with a physiologically acceptable vehicle and may optionally include an adjuvant to enhance the immune response of the host.
Therefore, it is one object of the present invention to provide an attenuated dengue virus composition comprising attenuated more than one dengue virus selected from the group consisting of dengue-1, dengue-2, dengue-3, and dengue-4, in any combination.
It is another object of the present invention to provide methods for stimulating the immune system of an individual to induce protection against dengue virus. These methods comprise administering to the individual an immunologically sufficient amount of dengue virus from all four serotypes which have been attenuated by serial passage.